Supercoiled DNA is far more dynamic than the 'Watson-Crick' double helix

The image shows the structure of the DNA calculated with the supercomputer simulations (in colour) superimposed upon the cryo-electron tomography data (in white or yellow). (There is no superimposition onto cryo-electron tomography data for the purple figure-8 shape.) You can see that the familiar double helix has been either simply bent into a circle or twisted into a figure-8. Credit: Thana Sutthibutpong

Researchers have imaged in unprecedented detail the three-dimensional structure of supercoiled DNA, revealing that its shape is much more dynamic than the well-known double helix.

Various DNA shapes, including figure-8s, were imaged using a powerful microscopy technique by researchers at the Baylor College of Medicine in the US, and then examined using supercomputer simulations run at the University of Leeds.

As reported online today in the journal Nature Communications, the simulations also show the dynamic nature of DNA, which constantly wiggles and morphs into different shapes - a far cry from the commonly held idea of a rigid and static double helix structure.

Improving our understanding of what DNA looks like when it is in the cell will help us to design better medicines, such as new antibiotics or more effective cancer chemotherapies.

Dr Sarah Harris from the School of Physics and Astronomy at the University of Leeds, who led the computer simulation research side of the study, said: "This is because the action of drug molecules relies on them recognising a specific molecular shape - much like a key fits a particular lock."

The double helix shape has a firm place in the public's collective consciousness. It is referenced in popular culture and often features in art and design. But the shape of DNA isn't always that simple.

Dr Harris said: "When Watson and Crick described the DNA double helix, they were looking at a tiny part of a real genome, only about one turn of the double helix. This is about 12 DNA 'base pairs', which are the building blocks of DNA that form the rungs of the helical ladder.

"Our study looks at DNA on a somewhat grander scale - several hundreds of base pairs - and even this relatively modest increase in size reveals a whole new richness in the behavior of the DNA molecule."

Supercomputer simulations show how the dynamic motion of the supercoiled DNA causes its shape to change constantly to form a myriad of structures. Credit: Thana Sutthibutpong

There are actually about 3 billion base pairs that make up the complete set of DNA instructions in humans. This is about a metre of DNA. This enormous string of molecular information has to be precisely organised by coiling it up tightly so that it can be squeezed into the nucleus of cells.

To study the structure of DNA when it is crammed into cells, the researchers needed to replicate this coiling of DNA.

Dr Lynn Zechiedrich, the corresponding author for the study from the Baylor College of Medicine, said: "You can't coil linear DNA and study it, so we had to make circles so the ends would trap the different degrees of winding."

To investigate how the winding changed what the circles looked like, the researchers wound and then unwound the tiny DNA circles - 10 million times shorter in length than the DNA contained within our cells - a single turn at a time.

The researchers devised a test to make sure that the tiny twisted up DNA circles that they made in the laboratory acted in the same way as the full-length DNA strands within our cells, when it is referred to as 'biologically active'.

They used an enzyme called 'human topoisomerase II alpha' that manipulates the twist of DNA. The test showed that the enzyme relieved the winding stress from all of the supercoiled circles, even the most coiled ones, which is its normal job in the human body. This result means that the DNA in the circles must look and act like the much longer DNA that the enzyme encounters in human cells.

Dr Rossitza Irobalieva, the co-lead author on the publication, who conducted the work while she was at Baylor, used 'cryo-electron tomography' - a powerful microscopy technique that involves freezing biologically active material - to provide the first three-dimensional images of individual circular DNA molecules. She saw that coiling the tiny DNA circles caused them to form a zoo of beautiful and unexpected shapes.

"Some of the circles had sharp bends, some were figure-8s, and others looked like handcuffs or racquets or even sewing needles. Some looked like rods because they were so coiled," said Dr Irobalieva.

The static images produced by the cryo-electron tomography were then compared to and matched with shapes generated in supercomputer simulations that were run at the University of Leeds. These simulated images provided a higher-resolution view of the DNA and show how its dynamic motion makes its shape constantly change to form a myriad of structures.

The cryo-electron tomography of the tiny DNA circles also revealed another surprise finding.

Base pairs in DNA are like a genetic alphabet, in which the letters on one side of the DNA double helix only pair with a particular letter on the other side. While the researchers expected to see the opening of base pairs - that is, the separation of the paired letters in the genetic alphabet - when the DNA was under-wound, they were surprised to see this opening for the over-wound DNA. This is because over-winding is supposed to make the DNA double helix stronger.

The researchers hypothesise that this disruption of base pairs may cause flexible hinges, allowing the DNA to bend sharply, perhaps helping to explain how a meter of DNA can be jammed into a single human cell.

Dr Harris concludes: "We are sure that supercomputers will play an increasingly important role in drug design. We are trying to do a puzzle with millions of pieces, and they all keep changing shape."

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37 comments

To study the structure of DNA when it is crammed into cells, the researchers needed to replicate this coiling of DNA.

The coiling is RNA-mediated. It is nutrient energy-dependent and perturbed by viruses. Viruses steal the energy that cells need to maintain their structural and functional integrity.

That fact was placed into the context of the microRNA/messenger RNA balance and adhesion proteins when researchers linked microRNAs and adhesion proteins to what is currently known about biophysically constrained nutrient-dependent RNA-mediated gene duplication and RNA-mediated amino acid substitutions.

The gene duplication and fixation of amino acid substitutions in the organized genomes of all genera link the physiology of reproduction to protein folding chemistry that typically protects DNA from virus-driven genomic entropy (i.e., cancer).

Actually, it's protein mediated. Supercoiling is controlled by histone interactions and mainly topoisomerases. Their function is to bind two strands of DNA, snip one, and reassemble it on the other side of the first strand. I wrote on this topic for genetics:

This is an open access article that attests to the fact you are a biologically uninformed science idiot.

http://dx.doi.org...omms9440Excerpt: "Our data provide relative comparisons of supercoiling-dependent twisted, writhed, curved, and kinked conformations and associated base exposure. Each of these structural features may be differentially recognized by the proteins, nucleic acids, and small molecules that modulate DNA metabolic processes."

anonymous_9001

I wrote on this topic for genetics:

You also wrote a review of my published work that linked everything known about biophysically constrained nutrient-dependent protein folding chemistry. Criticisms of the nutrient-dependent pheromone-controlled evolutionary model http://www.ncbi.n...4049134/

You still don't seem to realize who the Zechiedrich lab is laughing at.

Excerpt: "Our data provide relative comparisons of supercoiling-dependent twisted, writhed, curved, and kinked conformations and associated base exposure. Each of these structural features may be differentially recognized by the proteins, nucleic acids, and small molecules that modulate DNA metabolic processes."

That does not conflict with what I said.

Do you still think that the proteins evolved?

They change over generations, so yes. You can argue about the mechanisms within evolution all you want, but you just don't like that particular word and that's not my problem.

...you just don't like that particular word and that's not my problem.

Use of the definition in assumptions about biodiversity is the biggest problem that theorists have ever had to face.

No experimental evidence of biologically- based cause and effect links the conserved molecular mechanisms of nutrient-dependent base pair changes and RNA-mediated amino acid substitutions to the evolution of any species.

All the experimental evidence of biologically- based cause and effect links ecological variation to ecological adaptations that are nutrient-dependent and controlled by the physiology of reproduction in all living genera.

Use of the definition in assumptions about biodiversity is the biggest problem that theorists have ever had to face.

No experimental evidence of biologically- based cause and effect links the conserved molecular mechanisms of nutrient-dependent base pair changes and RNA-mediated amino acid substitutions to the evolution of any species.

All the experimental evidence of biologically- based cause and effect links ecological variation to ecological adaptations that are nutrient-dependent and controlled by the physiology of reproduction in all living genera.

Like I said before, YOU'RE the one caught up on definitions here. Evolution is simply change in a species over time. HOW that occurs is unrelated to the arbitrary name it's been given. Evolution includes adaptation. They're not mutually exclusive except to you because you have a pointless aversion to the word itself.

Koonin and others have been caught. They've had to change to claims about co-evolution, which is ecological adaptation. They are not willing to directly admit to touting pseudoscientific nonsense, but the indirect admission is perfectly clear in the context of required links from nutrient energy to base pair changes and RNA-mediated events linked from chromosomal rearrangements to biodiversity without the ridiculous neo-Darwinian theories.

Evolution includes adaptation. They're not mutually exclusive except to you...

Are you claiming Leski's E. coli ecologically adapted or that they evolved? Are you claiming that Tiffany Taylor's group reported a "re-evolved" flagellum (over the weekend) or an ecological adaptation?

News article excerpt: "The evolution of these key virulence determinants doesn't occur in the same way as in other pathogens. Instead of gradually changing by mutation, like the flu virus..."

See for comparison: Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution http://comments.s....1244730

Authors' comment: "The major antigenic changes of the influenza virus are primarily caused by a single amino acid near the receptor binding site."

My comment: See: Dobzhansky (1973)"... the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla. ( p. 127)"

What experimental evidence supports the claim that it took millions of years to link one amino acid substitution across all species?

What experimental evidence supports the claim that it took millions of years to link one amino acid substitution across all species?

That question is relevant to discussion of the findings reported here.

The claim that evolution of key virulence determinants in malaria doesn't occur via mutations as others have claimed it does in viruses (via gradual changes), has never been addressed with experimental evidence of biologically-based cause and effect.

Koel et al (2013) reported a single nutrient-dependent amino acid substitution links the major antigenic changes of the influenza virus to the need for protective yearly vaccinations.

That suggests the claims about nutrient-dependent base pair changes can be compared in the context of prevention and treatment of all virus-driven pathology.

Are you claiming Leski's E. coli ecologically adapted or that they evolved? Are you claiming that Tiffany Taylor's group reported a "re-evolved" flagellum (over the weekend) or an ecological adaptation?

They evolved THROUGH adaptation. Evolution and adaptation are not separate processes. Evolution is change over time and adaptation is a mechanism by which change over time occurs. There's no conflict here besides between you and the word "evolution".

The question is quite relevant considering you've used more words avoiding answering the question than a simple answer would require. A science based answer is approximately 4.5billion years. That is not controversial in science, it's only challenged by young earth creationists and there is absolutely nothing scientific about young earth creationism.

All serious scientists now realize that the only way to protect organized genomes from virus-driven pathology is via the elimination of nutrient stress and social stress that suppresses the innate immune system function, which was designed to ensure species survival via links from ecological variation to ecological adaptation.

The links are RNA-mediated and perturbed by the theft of nutrient energy by viruses.

Excerpt: "miRNA-induced gene-silencing approach holds great promise for selectively inhibiting virus-specific genes or host genes for the treatment of viral infections. Hence, the most fundamental challenge lies toward understanding the entire landscape of the miRNA-mediated host–virus interaction at the molecular level, which will lead toward the development of effective non-toxic antiviral therapy."

Re: The "Modern Synthesis" includes nothing about the role of viruses.

How can evolutionary theorists ever hope to catch up with the data on cell type differentiation now that serious scientists understand the links from base pairs to nutrient-dependent ecological adaptation in the context of microRNAs and amino acid substitutions?

"There is no mention at all of any biochemical pathways or enzymes that are involved in 'nutrient-dependent, pheromone-controlled' nucleotide or amino acid substitutions, so how changes in the DNA sequence are made in his model are entirely unexplained."

Rosalind Elsie Franklin (30 July 1920 – 16 April 1958)[1] was an English chemist and X-ray crystallographer who made contributions to the understanding of the fine molecular structures of DNA (deoxyribonucleic acid), RNA (ribonucleic acid), viruses, coal, and graphite.[2] Although her works on coal and viruses were appreciated in her lifetime, her DNA work posthumously achieved profound impact....

I'll ask again. Based on your science knowledge, what is the age of the Earth?

You don't know the age of the Earth either.

I've shown from Stellar model for example, that the calculated age of Stars is based entirely on assumptions which could easily be wrong. If you make different assumptions about starting composition, their calculated age changes. The discovery that the neutrino has mass will change the calculated age of stars. If Dark Matter is real the calculated age of Stars will be wrong, because nobody takes that into consideration, and it is impossible to tell how much of a star's mass is Dark Matter, if Dark Matter exists.

Dating the Earth or the Universe through the currently employed techniques is an almost completely futile endeavor.

I have shown that the universe could be 22Billion or more years old if you assume Relativity is entirely correct, however, I have proven that there are relevant flaws in Relativity, so the age changes.

Returners

Returners

"From nothing comes nothing" used to be an axiom. you took it for granted.

Then along comes atheism and tries to say it's okay for everything to come from nothing.

So I thought about reality in terms of sets, and I thought about nothing in terms of empty sets, and I thought about processes needed to turn nothing into something...since science is about proving ordered relationships and causes and effects and such.

It turns out that "from nothing comes nothing" is not an Axiom. It is the result of a PROOF based on the laws of mathematics.

It's very simple. "Nothing" would be an empty set, and it can't contain a process to convert itself into something, because an empty set is empty, obviously.

P, the process hypothetically needed to make something from nothing.

Nothing{}, Empty set.

P cannot be in Nothing{}, therefore the universe did not come from nothing.

You people are supposed to be smarter than this, but you have willfully darkened your heart.

Thanks. I suspect that if Linus Pauling was not still dead, he would have ended the threat to humans of Ebola viruses after noting that the organized genomes of frugivorous bats protected bats from virus-driven genomic entropy,probably via increased vitamin C content in their diet.

I've shown from Stellar model for example, that the calculated age of Stars is based entirely on assumptions which could easily be wrong.

You could help people like me by providing citations to support such claims, rather than citing scripture. Citing scripture will not open up the virus-perturbed minds of atheists and neither will facts.

But the facts may help others who are struggling with their faith in creation so that they are not led to become biologically uninformed science idiots by those who were taught to become biologically uninformed science idiots in past generations.

Did Pauling's ideas about the "triple helix" inadvertently address aspects of the biophysically constrained energy-dependent bonds that are perturbed when viruses steal the energy needed for proper protein folding?

If so, that means his ideas about nutrient-dependent quantum chemistry could have been followed to the conclusions that today link nutritional epigenetics and pharmacogenomics via metabolic networks and genetic networks in the context of works by the Zechiedrich lab and also in publications by Eshel Ben-Jacob's group or in his monographs.

It will be interesting to see whether the content of works by the Zechiedrich lab, Pauling, or Ben-Jacob are ever discussed by neo-Darwinian theorists in the context of the "re-evolved" bacterial flagellum. http://www.the-sc...ewiring/

God's just giving you a chance to realize that and repent. That's all.

The moderators at ScienceX sites take that chance away because they accept the ridiculous consensus of biologically uninformed theorists and claim that anything that is not mainstream "science" is pseudoscience.

Links to creationist literature are removed. That's how pseudoscientists managed to establish their consensus about evolution. Eliminate the claims of anyone who provides experimental evidence of top-down causation (e.g., virus perturbed protein folding linked to pathology) and theorists find it easier to convince the majority that their claims represent facts.

For comparison, "...learning about evolution is not the primary function of the decision, but rather to use it as a building block for students to learn more about their ecology." -- http://www.educat...olution/

"Structural diversity of supercoiled DNA" and the video about base pairs from the Zechiedrich lab are the best anti-evolutionist materials that I believe can be used to refute this type of pseudoscientific nonsense.

Top-down causation starts with nutrient-dependent changes in base pairs, not with mutated genes. Viruses link perturbed protein folding and mutated genes to all pathology, not to the evolution of any new species.

Rarely do sex researchers address the ongoing philosophical debate between canonical neo-Darwinism and Biblical creation. Perhaps this is because any debate between scientific theory and religion arises from distinctly different domains of cognitive thought. Does the acceptance of Darwin's theory represent the glorification of ..." [cont.]

[cont] "... Since all life does not beget diversified life, those who judge sexual preferences that do not seem to result in diversified life may be judging creation itself.

It is easy to understand how someone could judge a particular sexual preference, without thought. Unconscious affects that are manifest in the development of human sexual preferences are, by their nature, a part of diversified life that few people think about. What we think about human sexual preferences becomes less meaningful when we realize that most of sexual behavior is not what we cognitively think it should be. Indeed, the largest contributor to sexual preferences that are manifest in the sexual behavior of any species appears to be unconscious affect. This also appears to be the basis for diversified life."

If mutations are the basis for biodiversity, what does the claim of a mutated gene mean in the context of evolved "Male-to-Male Attraction."

Excerpt: ...we now understand something about how piRNAs are transcriptionally silencing their targets," said molecular geneticist Keith Slotkin of Ohio State University who was not involved in the work.

Slotkin was involved in this work: Gene Expression and Stress Response Mediated by the Epigenetic Regulation of a Transposable Element Small RNA http://journals.p....1002474

Others have since linked "Mechanisms of stress in the brain" http://www.nature...086.html to cell type differentiation in all individuals of all species via the conserved molecular mechanisms we detailed in our 1996 review.

What happened to all the biologically uninformed science idiots who have shown support for creationist perspectives via their inability to support the pseudoscientific nonsense touted by neo-Darwinian theorists.

Did they finally realize serious scientists must start with top-down causation and link anti-entropic energy to the creation of the first cell and virus-driven genomic entropy to all pathology?

If anyone has not realized what serious scientists already know about biologically-based cause and effect, see: A non-proteolytic role for ubiquitin in deadenylation of MHC-I mRNA by the RNA-binding E3-ligase MEX-3C http://dx.doi.org...omms9670

They conclude: "...the role of ubiquitin now extends beyond protein degradation to include the regulation and turnover of nucleic acids."

http://rna-mediated.com/Description: Here you will find information that links physics, chemistry, and molecular epigenetics via RNA-mediated events such as the de novo creation of olfactory receptor genes in order to encourage a public discussion of a paradigm shift.

Please provide an example of the pseudoscience creationist crap that you are reporting as PHISHING PSEUDOSCIENCE SITE or report yourself for trying to suppress any accurate representations of biologically-based cause and effect.

See also: Molecular Clocks and the Puzzle of RNA Virus Origins http://jvi.asm.or...93.shortExcerpt: "...in the case of the primate lentiviruses, amino acid residues that are highly variable in HIV are sometimes conserved in chimpanzee SIV (19), and this may have a significant effect on dating estimates."

That "conservation" differentiates gorillas from chimpanzees and modern humans via a single amino acid substitution, not millions of years of evolution.

PHISHING PSEUDOSCIENCE SITEpersonal owned site also - putting science or techno-jargon in the description doesn't mean it is a science site: the site also contains CREATIONIST links and arguments for CREATIONIST dogmaso long as you promote RELIGION as equivalent to SCIENCE then it is a PSEUDOSCIENCE SITE

Please provide an example of the pseudoscience creationist crap

start here: author/j-v-kohl/there is plenty of examples in your author posts, etcyour typical post has CREATIONIST dogmabut i am NOT opening your site unless protected- or by proxy (because of your PHISHING) and i am NOT spreading your stupidity and links here! you do that enough already!

trying to suppress any accurate representations of biologically-based cause and effect.

if you were promoting "accurate representations of biologically-based cause and effect", you would be able to link to original sources of REPUTABLE peer reviewed scientific journals... you wouldn't be trying to get people to see your personal site and you wouldn't be making claims and creationist stupidity like what is found on your site.

IF your site was scientific, it wouldn't contain hate/vilification of science (via CREATIONIST and PSEUDOSCIENCE literature you write/post) and it would not contain ANYTHING from ANY religious organization. period

the reason you link it is to SPAM, PHISH for data and TROLL... there is NO SCIENCE in the creationist movement: https://en.wikipe...Arkansas

that is not speculation or an opinion, it is a FACT, PROVEN IN COURTUPHELD BY THE SUPREME COURT OF THE USA

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